Cancer still remains one of the top leading causes of death in America. Recently, programmed cell death protein 1 (PD-1) blockades have been demonstrated to be highly effective against various types of cancer. By blocking PD-1 from binding with their ligands (PD-L1 and PD-L2), the “off” signal to the immune system is inhibited, hence reinvigorating the immune cells to kill tumor cells. To date, despite PD-L1 and PD-L2 both interacting with PD-1, research efforts have only been focused on developing anti-PD-L1 inhibitors. Therefore, the work of this honor project has focused on finding anti-PD-L2 peptides by phage display, with the purposes of expanding our cancer drug repertoire and combining anti-PD-L2 inhibitors with anti-PD-L1 drugs to achieve synergistic effects.
Chapter 1 gives an overview and background of the topics that will be covered in this honor project. We will first introduce the basic principles of immune-checkpoint blockade, current treatments, challenges, our solution, and finally details of our method peptide phage display. The research detailed in chapters 2 shows initial evidence of our peptide candidates binding to PD-L2 protein using phage display, plaque assay, and ELISA test. We observed significant phage enrichment after 5 rounds of bio-panning, indicating the survival phage library has high binding ability toward PD-L2, even after harsh washing steps. We later examined this potential binding using the ELISA test. Interestingly, peptides in the latter rounds of biopanning were found to have lower binding affinity to the initial peptide input. Lastly, in chapter 3 we discuss the limitations of this study and future directions to either improve the method protocol or to select a different target.
First Advisor Department
Second Advisor Department
Tran Phuoc, Chien, "Screening Anti-PD-L2 Peptides as Antitumor Ligands Using Phage Display" (2022). Honors Projects. 847.